To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, tolerability, (Pharmacokinetics) PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL). Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and to determine safety and tolerability. An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an intermittent dosing schedule (5 continuous days out of 7 days per week) and 3-6 subjects will be enrolled in subsequent dose levels. Dose escalation for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) (Storer, 1989) to establish initial toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
5 continuous days out of 7 days per week intermittent dosing
Local Institution - 002
Koto-ku, Tokyo, Japan
Local Institution - 003
Chikusa-ku, Japan
Local Institution - 001
Kashiwa, Japan
Number of Participants With Dose-Limiting Toxicities (DLTs)
NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs: * Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3 * Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting \> 7 days, Grade 4 thrombocytopenia lasting \> 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding * Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs * Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation period
Time frame: From first dose up to at least 28 days (Cycle 1)
Maximum Tolerated Dose (MTD)
The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D). MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03
Time frame: From first dose up to at least 28 days (Cycle 1)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03
Time frame: From first dose to 28 days post last dose of investigational product (Up to approximately 92 months)
Pharmacokinetic Parameters of CC-122: AUC0-t
Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t)
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Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: AUCtau
Area under the plasma concentration time-curve during a dosing interval (AUCtau)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: Cmax
Peak (maximum) plasma concentration (Cmax)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: Tmax
Time to maximum plasma concentration (Tmax)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: t1/2
Terminal half-life of CC-122 (t1/2)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: CL/F
Apparent clearance (CL/F)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Pharmacokinetic Parameters of CC-122: Vz/F
Apparent volume of distribution (Vz/F)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Accumulation Index of CC-122
Accumulation Index defined as AUCtau (Cycle 1 Day 10, 11 or 12)/AUCtau (Cycle 1 Day 1)
Time frame: 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days)
Best Overall Response (BOR)
BOR by investigator is defined according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma for NHL patients and Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for solid tumors patients. For NHL, complete remission (CR)=disappearance of all evidence of disease. Partial response (PR)=regression of measurable disease and no new sites. Stable disease (SD)=failure to attain CR/PR or PD. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir. For solid tumors, complete response (CR)=disappearance of all target and non-target lesions and no new lesions. PR=at least a 30% decrease in the sum of diameters of target lesions and no new lesions. SD=neither sufficient shrinkage to qualify for PR or increase to qualify for PD. PD=at least 20% increase in the sum of diameters of target lesions from nadir.
Time frame: From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)
Duration of Response (DoR)
DoR for NHL patients is defined as the time from the date when complete response (CR) or partial response (PR), whichever is first recorded are met, until the date when disease progression (PD) is first objectively documented, or the date of the last adequate tumor assessment when no disease progression is documented throughout the study according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR=disappearance of all evidence of disease. PR=regression of measurable disease and no new sites. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir.
Time frame: From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days)